The skin is the largest organ in the body and serves important functions that are necessary to life. The skin acts as a barrier to the invasion of various pathogens and toxic substances. Skin is composed of the two layers: the epidermis is the first layer; and the dermis is the layer below the epidermis.
However, because it must serve as a barrier to the ingress of pathogens and toxic materials, and the egress of physiologic fluids, the skin is highly impermeable. It must be impermeable to preserve its own integrity while at the same time maintaining the delicate dynamic electrolyte balance of the body. The skin must serve a containment function; it must also function as a microbial, chemical, radiation and thermal barrier.
A good deal of this impermeability of the skin results from the nature of one very thin layer created by normal developmental and physiological changes in the skin. After cells are formed in the basal layer, they begin to migrate toward the skin surface, until they are eventually sloughed off. As they undergo this migration, they become progressively more dehydrated and keratinized. When they reach the surface, just prior to being discarded, they form a thin layer of dense, metabolically inactive cells approximately ten microns (10-15 cells) thick. This layer is called the stratum corneum or the “cornified layer”. As a result of the high degree of keratinization of the cells which comprise the stratum corneum, a formidable barrier is created. Therefore, penetration via the nonpolar route, i.e., across the membrane of these cells, remains most difficult.
The problem is even more difficult when trying to deliver pharmaceutical agents through the unguis, the horny cutaneous plates on the dorsal surface of the distal end of the terminal phalanx of a finger or toe (fingernails and toenails). They are made up of flattened epithelial scales developed from specialized epithelial cells called the matrix. The thick and hardened nature of nails renders access through, and to the area below, nearly impossible with current topical formulations. The subject of the present disclosure has the advantage of being able to delivery pharmaceutical agents through the unguis to heretofore minimally accessible disease targets.
Accordingly, in an effort to take advantage of this route of administration and overcome the obstacles the skin and nails naturally provide, the art has turned to the use of specifically selected vehicles and carriers into which the pharmaceutical active is incorporated so that the vehicle or carrier aids in, or at a minimum does not adversely affect, the penetration of the selected active agent. The art recognizes that to a vast degree the rate of percutaneous delivery of a pharmaceutical active can be significantly decreased by the selection of an improper vehicle.
Because of the ease of access, dynamics of application, large surface area, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the treatment, the delivery of pharmaceutically-active agents through the skin has long been a promising concept. This is true whether the bioavailability desired is systemic or dermal, regional or local.
The advantages of this form of delivery include, but are not limited to: avoidance of the risks associated with parenteral treatment; elimination of the inconveniences of parenteral treatment; avoidance of the variable rates of absorption and metabolism inherent in oral treatment; increasing the continuity of drug administration by permitting delivery of agents with short biological half-lives; and elimination of gastrointestinal irritation resulting from exposing the gastrointestinal tract to pharmaceutical actives, preservatives, tableting agents, and the like. Most importantly, topical delivery possesses the potential for effectively treating conditions which are local in nature (or which exhibit local manifestations), systemically as well as locally with the same treatment regimen. Thus, effective compositions to deliver pharmaceutical agents are highly sought after.
Although various compositions have been suggested for the precutaneous delivery of certain pharmaceutically active agents, a need exists for achieving enhanced delivery of cosmetic and pharmaceutical agents to the skin for local treatment of skin conditions and diseases. In particular, the composition should be easy to apply topically in a quantitative amount, to allow the active agent to rapidly permeate the skin to get where the agent is needed, to have a pleasant odor and appearance, and to not require cleansing to remove the agent.
This combination of these desired characteristics is difficult to achieve.